HUMAN IMMUNODEFICIENCY VIRUS

Question 1

Types of HIV:

Answer 1

1. HIV-1 - more pathogenic stain
2. HIV-2 - less pathogenic, lower transmission rate

Question 2

Former names of HIV-1:

Answer 2

• HTLV-III
• Lymphadenopathy-associated virus (LAV)
• AIDS-associated retrovirus (ARV)

Question 3

HIV-1 groups:

Answer 3

1. Group M (the main or major group)
2. Group N (the non-M/ non-O, or New group)
3. Group O (the outlier group)

Question 4

How many subtypes does HIV-1 Group M have?

Answer 4

9 subtypes
- A
- B
- C
- D
- F, G, H, J, and K

Question 5

Most predominant subtype in the US and Europe

Answer 5

Subtype B

Question 6

Most predominant subtype worldwide

Answer 6

Subtype C

Question 7

Encoded by the ENV gene (envelope gene); serves for attachment of HIV to CD4 cells:

Answer 7

Gp41/Gp120 complex

Question 8

The protein that traverses the membrane:

Answer 8

Gp41

Question 9

A knoblike structure attached to Gp41:

Answer 9

Gp120

Question 10

Nucleocapsid core protein of the virus; encoded by the gag gene (group antigen)

Answer 10

p24

Question 11

Matrix shell protein; encoded by the gag gene 9group antigen)

Answer 11

p17

Question 12

Transcribes viral RNA to DNA:

Answer 12

Reverse transcriptase

Question 13

Reverse transcriptase is encoded by ____ gene

Answer 13

pol gene (polymerase gene)

Question 14

Standard screening test for HIV antibody:

Answer 14

ELISA (Enzyme-Link Immunosorbent Assay)

Question 15

Confirmatory test for HIV:

Answer 15

Western Blot ASsay

Question 16

Western Blot Assay detects _____ Abs specific to _____

Answer 16

Western Blot Assay detects IgG Abs specific to HIV antigens

Question 17

In Western Blot Assay, the separated HIV-1 proteins are transferred to a _______.

Answer 17

nitrocellulose membrane

Question 18

CDC CRITERIA FOR POSITIVE INTERPRETATION OF WESTERN BLOT TEST:

Answer 18

Presence of at least 2 out of 3 bands to:
- p24
- Gp41
- Gp120/160

Question 19

What is the earliest HIV serological marker to appear?

Answer 19

p24

note: High in initial weeks of infection during the early burst of viral replication, then become undetectable as antibody to p24 develops appears about 1 week before the appearance of HIV antibody during the acute stage of infection, allowing for slightly earlier detection of the virus.

Question 20

All of the following describe HIV except

a. it possesses an outer envelope.
b. it contains an inner core with p24 antigen.
c. it contains DNA as its nucleic acid.
d. it is a member of the retrovirus family

Answer 20

c. it contains DNA as its nucleic acid.

HIV characteristics:
1. Outer envelope (a): Correct, derived from host cell membrane.
2. Inner core with p24 antigen (b): Correct, core protein.
3. Member of retrovirus family (d): Correct, utilizes reverse transcription.

However, HIV’s genetic material consists of:

• Single-stranded RNA (+) sense

Not DNA. Reverse transcriptase converts RNA to double-stranded DNA during replication.

Question 21

HIV virions bind to host T cells through which receptors?

a. CD4 and CD8
b. CD4 and the IL-2 receptor
c. CD4 and CCR5
d. CD8 and CCR2

Answer 21

c. CD4 and CCR5.

HIV-1 virions bind to host T cells via:

Primary Receptor
1. CD4 (cluster of differentiation 4): Primary receptor, essential for viral attachment.

Co-Receptors
1. CCR5 (CC chemokine receptor 5): Primary co-receptor, facilitating viral entry.
2. CXCR4: Alternate co-receptor, utilized by some HIV-1 strains.

CD4+ T cells (helper T cells) are primary targets.

Question 22

Suppose a combination immunoassay to screen for HIV infection was positive, but the confirmatory test was negative. Which of the following tests should be performed?

a. p24 antibody
b. Western blot
c. PCR for HIV-1 RNA
d. No further testing is needed, and the screening test should be interpreted as a false positive.

Answer 22

d. No further testing is needed, and the screening test should be interpreted as a false positive.

When:
1. Combination immunoassay (screening) is positive.
2. Confirmatory test (e.g., Western blot) is negative.

Guidelines recommend:
1. No further testing.
2. Interpret screening result as false positive.

Exceptions:
1. Recent exposure (<3 months).
2. Immunocompromised individuals.
3. Clinical suspicion.

In these cases, repeat testing or PCR may be considered.

Question 23

Which of the following is typical of the latent stage of HIV infection?

a. Proviral DNA is attached to cellular DNA.
b. Large numbers of viral particles are synthesized.
c. A large amount of viral RNA is synthesized.
d. Viral particles with no envelope are produced.

Answer 23

a. Proviral DNA is attached to cellular DNA.

Characteristics of HIV latent stage:

Key Features

1. Proviral DNA integration: HIV genetic material combines with host cell DNA.
2. Low or undetectable viral replication.
3. Minimal viral transcription.
4. No active viral production.
5. Immune system evasion.

Latency Sites
1. Resting memory CD4+ T cells.
2. Macrophages.
3. Dendritic cells.

Other Options
1. b & c: High viral replication occurs during acute infection, not latency.
2. d: Viral particles require an envelope for infectivity.

Question 24

The decrease in T-cell numbers in HIV-infected individuals is caused by

a. lysis of host T cells by replicating virus.
b. fusion of the T cells to form syncytia.
c. killing of the T cells by HIV-specific cytotoxic T cells.
d. all of the above.

Answer 24

d. all of the above.

Explanation
The decrease in T-cell numbers in HIV-infected individuals is multifactorial:

1. Lysis of host T cells by replicating virus (a): HIV replication causes direct cellular damage.
2. Fusion of T cells to form syncytia (b): HIV-infected cells fuse, leading to giant cells and subsequent cell death.
3. Killing of T cells by HIV-specific cytotoxic T cells (c): Immune response against infected cells.

Additional mechanisms:
- Apoptosis (programmed cell death)
- Immune exhaustion
- Dysfunction of immune cells
- Destruction of lymphoid tissues

Question 25

The most common means of HIV transmission worldwide is through a. blood transfusions. b. intimate sexual contact. c. sharing of needles in intravenous drug use. d. transplacental passage of the virus.

Answer 25

b. intimate sexual contact. According to UNAIDS and the World Health Organization (WHO), the primary modes of HIV transmission globally are: Sexual Transmission (approx. 80-85%) 1. Heterosexual contact (majority) 2. Homosexual contact Other Modes 1. Sharing needles/syringes (injectable drug use): 5-10% 2. Mother-to-child transmission (transplacental, breastfeeding): 5-7% 3. Blood transfusions: rare (due to screening) 4. Occupational exposure (healthcare workers): rare

Question 26

The drug zidovudine is an example of a a. nucleoside analogue reverse-transcriptase inhibitor. b. nonnucleoside reverse-transcriptase inhibitor. c. protease inhibitor. d. fusion inhibitor.

Answer 26

a. nucleoside analogue reverse-transcriptase inhibitor (NRTI). Zidovudine (AZT) works by: Mechanism 1. Mimicking natural nucleosides. 2. Inhibiting HIV's reverse transcriptase enzyme. 3. Blocking viral RNA conversion to DNA. Classifications 1. NRTIs (e.g., zidovudine, lamivudine). 2. Non-NRTIs (e.g., nevirapine, efavirenz). 3. Protease inhibitors (e.g., lopinavir, ritonavir). 4. Fusion inhibitors (e.g., enfuvirtide). Clinical Use Zidovudine: 1. Treats HIV-1 infection. 2. Prevents mother-to-child transmission. 3. Part of antiretroviral therapy (ART) regimens.

Question 27

False-negative test results in a laboratory test for HIV antibody may occur because of a. heat inactivation of the serum before testing. b. collection of the test sample before seroconversion. c. interference by autoantibodies. d. recent exposure to certain vaccines.

Answer 27

b. collection of the test sample before seroconversion. False-negative HIV antibody test results can occur due to: Timing Issues 1. Window period: Sampling before seroconversion (average 3-4 weeks, up to 3 months). 2. Early infection: Antibody levels may be undetectable. Technical Factors 1. Insufficient sensitivity: Test limitations. 2. Sample handling errors: Improper storage, handling or transportation. Biological Factors 1. Immunosuppression: Weakened immune response. 2. Coinfections: Certain infections (e.g., tuberculosis) affecting antibody production. Rare Causes 1. Autoantibodies: Interfering with assay. 2. Vaccine interference: Uncommon. To minimize false-negatives: 1. Repeat testing after 3-6 months. 2. Use combination assays (antibody/antigen). 3. Consider viral load (PCR) testing.

Question 28

Which of the following combinations of bands would represent a positive Western blot for HIV antibody? a. p24 and p55 b. p24 and p31 c. gp41 and gp120 d. p31 and p55

Answer 28

c. gp41 and gp120. A positive Western blot for HIV antibody typically requires: Required Bands 1. gp41 (envelope protein) 2. gp120 (envelope protein) Optional Supporting Bands 1. p24 (core protein) 2. p31 (core protein) Interpretation 1. Two or more specific HIV protein bands (gp41, gp120, p24, p31) confirm positivity. 2. Single-band presence or non-specific reactivity requires re-testing. Western Blot Criteria 1. CDC: Two or more specific bands. 2. WHO: At least two bands (gp41, gp120, or p24).

Question 29

The fourth-generation combination immunoassays for HIV detect a. HIV-1 and HIV-2 antigens. b. HIV-1 and HIV-2 antibodies. c. p24 antigen. d. HIV-1 antibodies, HIV-2 antibodies, and p24 antigen.

Answer 29

d. HIV-1 antibodies, HIV-2 antibodies, and p24 antigen. Fourth-generation combination immunoassays (CIAs) detect: 1. HIV-1 antibodies (IgM/IgG) 2. HIV-2 antibodies (IgM/IgG) 3. p24 antigen (HIV-1) These combination assays: 1. Improve sensitivity and specificity. 2. Reduce window period (average 14-24 days). 3. Enhance detection of acute infection. Components: 1. Enzyme-linked immunosorbent assay (ELISA) 2. Chemiluminescent immunoassay (CLIA) 3. Immunochromatographic tests

Question 30

The conjugate used in fourth-generation immunoassays for HIV consists of labeled a. anti-human immunoglobulin. b. HIV-1- and HIV-2-specific antibodies. c. HIV-1- and HIV-2-specific antigens. d. HIV-1- and HIV-2-specific antigens plus antibody to p24.

Answer 30

d. HIV-1- and HIV-2-specific antigens plus antibody to p24. Fourth-generation HIV assays combine: 1. HIV-1/HIV-2 antigens 2. Anti-p24 antibody Enabling simultaneous detection: 1. HIV-1/HIV-2 antibodies 2. p24 antigen Improving sensitivity, specificity and reducing window period.

Question 31

The characteristic laboratory finding in HIV infection is decreased a. numbers of CD4 T cells. b. numbers of CD8 T cells. c. numbers of CD20 B cells. d. immunoglobulins.

Answer 31

a. numbers of CD4 T cells. HIV infection's hallmark laboratory finding is: Decreased CD4+ T-cell count 1. CD4+ T-cell depletion: Progressive decline in CD4+ T-cell numbers and percentage. 2. CD4/CD8 ratio reversal: Normal ratio (1:2) reverses due to decreased CD4+ and increased CD8+ T cells. Other laboratory findings: 1. Increased viral load (HIV RNA) 2. Decreased lymphocyte count 3. Elevated liver enzymes 4. Thrombocytopenia (low platelet count) Monitoring CD4+ T-cell count and viral load helps assess: 1. Disease progression 2. Treatment efficacy 3. Immune system recovery

Question 32

Which of the following tests is currently recommended by the CDC to confirm a positive screening test result for HIV infection? a. Rapid test for HIV-1 and HIV-2 antibodies b. Western blot c. Molecular testing for HIV RNA d. HIV viral culture

Answer 32

a. Rapid test for HIV-1 and HIV-2 antibodies The CDC guidelines replaced the Western blot with a rapid HIV-1/HIV-2 antibody test as the standard method for confirming positive screening results. Rapid tests are more suitable for confirmation because they can be performed more quickly, detect infection earlier, reduce the incidence of indeterminate results, and detect HIV-1 and HIV-2 infections simultaneously. However, HIV-1 Western blot testing still available in some reference laboratories and may be used as a confirmatory method in special situations, such as the testing of dried blood or urine or of samples that have indeterminate antibody screening results and test negative for HIV-1 RNA. (Stevens 5th Edition)

Question 33

Which of the following tests would give the least reliable results in a 2-month-old infant? a. CD4 T-cell count b. ELISA for HIV antibody c. PCR for HIV proviral DNA d. p24 antigen

Answer 33

b. ELISA for HIV antibody. In infants <18 months, maternal HIV antibodies can cause: False-Positive Results 1. ELISA (HIV antibody test) 2. Rapid tests Preferred Tests for Infants <18 months 1. PCR for HIV proviral DNA (c) 2. HIV viral culture 3. p24 antigen test (d) Why CD4 T-cell count (a) is unreliable 1. Variability in normal ranges 2. Immature immune system

Question 34

Which of the following measurements is/are routinely used to monitor patients with HIV infection who are undergoing antiretroviral therapy? a. HIV antibody titer b. p24 antigen levels c. CD4 T-cell and CD8 T-cell counts d. CD4 T-cell count and HIV RNA copy number

Answer 34

d. CD4 T-cell count and HIV RNA copy number These measurements monitor: CD4 T-cell Count 1. Immune system recovery 2. Treatment efficacy 3. Opportunistic infection risk HIV RNA Copy Number (Viral Load) 1. Viral replication 2. Treatment response 3. Resistance development 4. Disease progression Less commonly used: b. p24 antigen levels (acute infection/diagnosis) Not routinely used: a. HIV antibody titer (diagnosis, not monitoring c. CD8 T-cell counts (c) provide limited clinical utility.